DENV Inhibits Type I IFN Production in Infected Cells by Cleaving Human STING

Dengue virus (DENV) is a pathogen with a high impact on human health. It replicates in a wide range of cells involved in the immune response. To efficiently infect humans, DENV must evade or inhibit fundamental elements of the innate immune system, namely the type I interferon response. DENV circumvents the host immune response by expressing proteins that antagonize the cellular innate immunity. We have recently documented the inhibition of type I IFN production by the proteolytic activity of DENV NS2B3 protease complex in human monocyte derived dendritic cells (MDDCs). In the present report we identify the human adaptor molecule STING as a target of the NS2B3 protease complex. We characterize the mechanism of inhibition of type I IFN production in primary human MDDCs by this viral factor. Using different human and mouse primary cells lacking STING, we show enhanced DENV replication. Conversely, mutated versions of STING that cannot be cleaved by the DENV NS2B3 protease induced higher levels of type I IFN after infection with DENV. Additionally, we show that DENV NS2B3 is not able to degrade the mouse version of STING, a phenomenon that severely restricts the replication of DENV in mouse cells, suggesting that STING plays a key role in the inhibition of DENV infection and spread in mice.     

ANALYSIS OF ANCIENT DNA FROM FOSSIL CORALLINES (CORALLINALES,RHODOPHYTA)1

The field of molecular paleontology has recently made significant contributions to anthropology and biology. Hundreds of ancient DNA studies have been published, but none has targeted fossil coralline algae. Using regions of the SSU gene, we analyzed rDNA from fossil coralline algae of varying ages and states of preservation from Spain, Papua New Guinea (PNG), and the Great Barrier Reef (GBR). Specimens from PNG, GBR, and some localities from Spain did not contain endogenous ancient DNA. Reproducible sequence data were obtained from specimens ～550 years old from near Cadiz, Spain, and from rocky‐shore deposits in Carboneras, Almeria Province of Spain (～78,000 years before present [YBP]). Based on BLAST searches and a phylogenetic analysis of sequences, an undescribed coralline alga belonging to the Melobesioideae was discovered in the Carboneras material as well as the following coralline genera: Jania, Lithophyllum, Lithothamnion, Mesophyllum, and Phymatolithon. DNA from fleshy brown and red macroalgae was also discovered in the specimens from Carboneras. The coralline algae identified using molecular techniques were in agreement with those based on morphological methods. The identified taxa are common in the present‐day southeastern Spain littoral zone. Amino acid racemization, concentration ratios, and specific concentrations failed to show a correlation between biomolecular preservation and PCR amplification success. Results suggest that molecular investigations on fossil algae, although limited by technical difficulties, are feasible. Validity of our results was established using authentication criteria and a self‐critical approach to compliance.     

Minoxidil prevents 3,4-methylenedioxymethamphetamine-induced serotonin depletions: role of mitochondrial ATP-sensitive potassium channels, Akt and ERK

Preconditioning has emerged as a valid strategy against different neurotoxic insults. Although the mechanisms underlying preconditioning are not fully understood, the activation of ATP-sensitive potassium (KATP) channels has been proposed to play a pivotal role in neuronal preconditioning. In the present work we examine whether minoxidil a KATP channel activator protects against the long-term toxicity caused by the amphetamine derivative 3,4-methylenedioxymethamphetamine (MDMA) in rats. Our data show that intrastriatal administration of minoxidil prevents MDMA-induced long-term indole depletions in the rat striatum. This effect was not related to an effect on core temperature, as pre-treatment with minoxidil did not significantly alter MDMA-induced hyperthermia. Taking into account that minoxidil opens both sarcolemmal and mitochondrial KATP channels, we examined the role of each type of channels in the protective effects of minoxidil using specific inhibitors. The administration of HMR-1098, a blocker of the sarcolemmal KATP channels, along with minoxidil did not affect the protection afforded by the latter. On the contrary the selective mitochondrial KATP channel blocker 5-hydroxydecanoic acid completely reversed the protection afforded by minoxidil, thereby implicating the involvement of mitochondrial (but not sarcolemmal) KATP channels. Furthermore our data show the participation of Akt and extracellular signal-regulated kinases in minoxidil-afforded protection. Intrastriatal administration of wortmannin or PD98059 (inhibitors of phosphatidylinositol-3-kinase and mitogen-activated protein kinase/extracellular regulated protein kinase, respectively), along with minoxidil abolished the protective effect of minoxidil against the serotonergic toxicity caused by MDMA. These results demonstrate that minoxidil by opening mitochondrial KATP channels completely prevents MDMA toxicity and that Akt and MAP kinases are involved in minoxidil-afforded neuroprotection.     

Mapping of Genomic Regions (Quantitative Trait Loci) Controlling Production and Quality in Industrial Cultures of the Edible Basidiomycete Pleurotus ostreatus

Industrial production of the edible basidiomycete Pleurotus ostreatus (oyster mushroom) is based on a solid fermentation process in which a limited number of selected strains are used. Optimization of industrial mushroom production depends on improving the culture process and breeding new strains with higher yields and productivities. Traditionally, fungal breeding has been carried out by an empirical trial and error process. In this study, we used a different approach by mapping quantitative trait loci (QTLs) controlling culture production and quality within the framework of the genetic linkage map of P. ostreatus. Ten production traits and four quality traits were studied and mapped. The production QTLs identified explain nearly one-half of the production variation. More interestingly, a single QTL mapping to the highly polymorphic chromosome VII appears to be involved in control of all the productivity traits studied. Quality QTLs appear to be scattered across the genome and to have less effect on the variation of the corresponding traits. Moreover, some of the new hybrid strains constructed in the course of our experiments had production or quality values higher than those of the parents or other commercial strains. This approach opens the possibility of marker-assisted selection and breeding of new industrial strains of this fungus.     

The distribution of nuclear mass, volume and dimensions

Our own measurements and a review of measurements presented in the literature showed that the mass, volume and dimensions of cell nuclei are distributed with a skew towards higher values, a distribution that can best be described as lognormal. The practical consequences of this finding suggest that the measurements of mass and of size should be plotted on a logarithmic scale while DNA values are appropriately presented on a linear scale. The distribution of DNA values of normal cells represents errors introduced by random disturbances in preparations and measurements.     

Reliability of Health-Related Physical Fitness Tests among Colombian Children and Adolescents: The FUPRECOL Study

Substantial evidence indicates that youth physical fitness levels are an important marker of lifestyle and cardio-metabolic health profiles and predict future risk of chronic diseases. The reliability physical fitness tests have not been explored in Latino-American youth population. This study’s aim was to examine the reliability of health-related physical fitness tests that were used in the Colombian health promotion “Fuprecol study”. Participants were 229 Colombian youth (boys n = 124 and girls n = 105) aged 9 to 17.9 years old. Five components of health-related physical fitness were measured: 1) morphological component: height, weight, body mass index (BMI), waist circumference, triceps skinfold, subscapular skinfold, and body fat (%) via impedance; 2) musculoskeletal component: handgrip and standing long jump test; 3) motor component: speed/agility test (4x10 m shuttle run); 4) flexibility component (hamstring and lumbar extensibility, sit-and-reach test); 5) cardiorespiratory component: 20-meter shuttle-run test (SRT) to estimate maximal oxygen consumption. The tests were performed two times, 1 week apart on the same day of the week, except for the SRT which was performed only once. Intra-observer technical errors of measurement (TEMs) and inter-rater (reliability) were assessed in the morphological component. Reliability for the Musculoskeletal, motor and cardiorespiratory fitness components was examined using Bland–Altman tests. For the morphological component, TEMs were small and reliability was greater than 95% of all cases. For the musculoskeletal, motor, flexibility and cardiorespiratory components, we found adequate reliability patterns in terms of systematic errors (bias) and random error (95% limits of agreement). When the fitness assessments were performed twice, the systematic error was nearly 0 for all tests, except for the sit and reach (mean difference: -1.03% [95% CI = -4.35% to -2.28%]. The results from this study indicate that the “Fuprecol study” health-related physical fitness battery, administered by physical education teachers, was reliable for measuring health-related components of fitness in children and adolescents aged 9–17.9 years old in a school setting in Colombia.